CDH1 methylation and expression of E-cadherin and other markers in breast cancer

Authors

  • Luiz Fernando de Queiroz Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Programa de Pós-Graduação em Anatomia Patológica, Departamento de Patologia – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0002-6139-0597
  • Marcelo Soares da Mota e Silva Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Patologia – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0003-0981-5233
  • Fernando Colonna Rosman Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Patologia – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0003-4801-4391
  • Siane Lopes Bittencourt Rosas Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Clínica Médica – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0002-4814-0868
  • Heitor Siffert Pereira de Souza Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Clínica Médica – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0002-3647-7324
  • Maria da Glória da Costa Carvalho Universidade Federal do Rio de Janeiro, Faculdade de Medicina, Departamento de Patologia – Rio de Janeiro (RJ), Brazil. https://orcid.org/0000-0001-5890-8095

DOI:

https://doi.org/10.29289/2594539420240006%20

Keywords:

cadherin-1, methylation, breast neoplasms, immunohistochemistry

Abstract

Introduction: E-cadherin, encoded by the CDH1 gene, is a glycoprotein involved in cell adhesion, and the methylation of CDH1 can prevent the protein expression favoring tumor invasion. This study investigated the methylation of CDH1 in the DNA extracted from tumor and non-tumor tissues of breast cancer patients. In addition, the expression of E-cadherin, human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), progesterone receptor (PR), and the marker of proliferation Ki-67 (Ki-67) was analyzed by immunohistochemistry. Methods: Samples of tumor and non-tumor breast tissues were collected from 15 women diagnosed with breast carcinoma at the time of mastectomy to analyze CDH1 methylation. The DNA was extracted, modified by the sodium bisulfite method, and amplified by polymerase chain reaction (PCR). The expression of E-cadherin, HER-2, ER, PR, and Ki-67 was evaluated by immunohistochemistry. Results: All the 15 patients had CDH1 methylation in the tumor tissue, and nine had CDH1 methylation in the non-tumor breast tissue. The immunohistochemical analysis showed that one patient had E-cadherin expression, three had HER-2, five had ER, six had PR, and nine had Ki-67. Conclusions: Our findings suggest that CDH1 gene methylation prevented E-cadherin expression in breast tumors once only one of the nine patients tested by immunohistochemical analysis showed the protein. The methylation of CDH1 in non-tumor breast tissues observed in nine patients may suggest the presence of infiltrating neoplastic cells or non-neoplastic genetically transformed cells.

Downloads

Download data is not yet available.

References

1. Kaszak I, Witkowska-Piłaszewicz O, Niewiadomska Z, Dworecka-Kaszak B, Toka FN, Jurka P. Role of cadherins in cancer-a review. Int J Mol Sci. 2020;21(20):7624. https://doi.org/10.3390/ijms21207624

2. Bücker L, Lehmann U. CDH1 (E-cadherin) gene methylation in human breast cancer: critical appraisal of a long and twisted story. Cancers (Basel). 2022;14(18):4377. https://doi.org/10.3390/cancers14184377

3. Maker A, Gumbiner BM. Reconstitution of the full transmembrane cadherin-catenin complex. Protein Expr Purif. 2022;193:106056. https://doi.org/10.1016/j.pep.2022.106056

4. Janiszewska M, Primi MC, Izard T. Cell adhesion in cancer: beyond the migration of single cells. J Biol Chem. 2020;295(8):2495-505. https://doi.org/10.1074/jbc.REV119.007759

5. Alexander J, Mariani O, Meaudre C, Fuhrmann L, Xiao H, Naidoo K, et al. Assessment of the molecular heterogeneity of e-cadherin expression in invasive lobular breast cancer. Cancers (Basel). 2022;14(2):295. https://doi.org/10.3390/cancers14020295

6. Shargh SA, Sakizli M, Khalaj V, Movafagh A, Yazdi H, Hagigatjou E, et al. Downregulation of E-cadherin expression in breast cancer by promoter hypermethylation and its relation with progression and prognosis of tumor. Med Oncol. 2014;31(11):250. https://doi.org/10.1007/s12032-014-0250-y

7. Clusan L, Ferrière F, Flouriot G, Pakdel F. A basic review on estrogen receptor signaling pathways in breast cancer. Int J Mol Sci. 2023;24(7):6834. https://doi.org/10.3390/ijms24076834

8. Scabia V, Ayyanan A, De Martino F, Agnoletto A, Battista L, Laszlo C, et al. Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor. Nat Commun. 2022;13(1):3127. https://doi.org/10.1038/s41467-022-30898-0

9. Li Z, Wei H, Li S, Wu P, Mao X. The role of progesterone receptors in breast cancer. Drug Des Devel Ther. 2022;16:305-14. https://doi.org/10.2147/DDDT.S336643

10. Ahn S, Woo JW, Lee K, Park SY. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathol Transl Med. 2020;54(1):34-44. https://doi.org/10.4132/jptm.2019.11.03

11. Davey MG, Hynes SO, Kerin MJ, Miller N, Lowery AJ. Ki-67 as a prognostic biomarker in invasive breast cancer. Cancers (Basel). 2021;13(17):4455. https://doi.org/10.3390/cancers13174455

12. Mccormick TM, Carvalho CES, Bravo Neto GP, Carvalho MGC. Comparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer. Rev Col Bras Cir. 2018;46(1):e2068. https://doi.org/10.1590/0100-6991e-20192068

13. Pestaner JP, Bibbo M, Bobroski L, Seshamma T, Bagasra O. Potential of the in situ polymerase chain reaction in diagnostic cytology. Acta Cytol. 1994;38(5):676-80. PMID: 8091896.

14. Graff JR, Herman JG, Myöhänen S, Baylin SB, Vertino PM. Mapping patterns of CpG island methylation in normal and neoplastic cells implicates both upstream and downstream regions in de novo methylation. J Biol Chem. 1997;272(35):22322-9. https://doi.org/10.1074/jbc.272.35.22322

15. Silva MM, Fonseca CO, Moura-Neto R, Carvalho JF, Quirico-Santos T, Carvalho MG. Influence of GSTM1 and GSTT1 polymorphisms on the survival rate of patients with malignant glioma under perillyl alcohol-based therapy. Genet Mol Res. 2013;12(2):1621-30. https://doi.org/10.4238/2013.May.14.2

16. Corso G, Figueiredo J, De Angelis SP, Corso F, Girardi A, Pereira J, et al. E-cadherin deregulation in breast cancer. J Cell Mol Med. 2020;24(11):5930-6. https://doi.org/10.1111/jcmm.15140

17. De Santo I, McCartney A, Migliaccio I, Di Leo A, Malorni L. The emerging role of ESR1 mutations in luminal breast cancer as a prognostic and predictive biomarker of response to endocrine therapy. Cancers (Basel). 2019;11(12):1894. https://doi.org/10.3390/cancers11121894

18. Derakhshan F, Reis-Filho JS. Pathogenesis of triple-negative breast cancer. Annu Rev Pathol. 2022;17:181-204. https://doi.org/10.1146/annurev-pathol-042420-093238

19. Rivera-Franco MM, Leon-Rodriguez E. Delays in breast cancer detection and treatment in developing countries. Breast Cancer (Auckl). 2018;12:1178223417752677. https://doi.org/10.1177/1178223417752677

Downloads

Published

2025-11-13

How to Cite

Queiroz, L. F. de, Silva, M. S. da M. e, Rosman, F. C., Rosas, S. L. B., Souza, H. S. P. de, & Carvalho, M. da G. da C. (2025). CDH1 methylation and expression of E-cadherin and other markers in breast cancer . Mastology, 34. https://doi.org/10.29289/2594539420240006

Issue

Vol. 34 (2024)

Section

Original Articles

License

Copyright (c) 2025 Luiz Fernando de Queiroz, Marcelo Soares da Mota e Silva, Fernando Colonna Rosman, Siane Lopes Bittencourt Rosas, Heitor Siffert Pereira de Souza, Maria da Glória da Costa Carvalho

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.